Short answer: Leqvio (inclisiran) is an siRNA aimed at PCSK9, given by a healthcare professional at the start, at 3 months, then every 6 months.1 Repatha (evolocumab) is a PCSK9 inhibitor injected at home every 2 weeks or once a month.2 Both lower LDL cholesterol; only Repatha's label is approved to lower heart-event risk. Neither label compares the two.
| Leqvio | Repatha | |
|---|---|---|
| Drug | Inclisiran, a small interfering RNA (siRNA) directed to PCSK91 | Evolocumab, a PCSK9 inhibitor2 |
| Approved for | Lower LDL in adults, in HeFH from age 12, and in children 12 and older with HoFH1 | Lower heart-event risk in adults at increased risk; lower LDL in adults, and in HeFH and HoFH from age 102 |
| Who gives it | A healthcare professional1 | You or a caregiver at home, after training2 |
| Schedule | 284 mg at the start, at 3 months, then every 6 months1 | 140 mg every 2 weeks or 420 mg once a month2 |
| LDL change vs placebo | -52%, -50% and -48% at day 510 (ORION-10, ORION-11, ORION-9)1 | -71% and -63% at week 12 (LAPLACE-2); -57% at week 72 (FOURIER)2 |
| Heart outcome trial in the label | None1 | FOURIER: 9.8% vs 11.3% on placebo; VESALIUS-CV: 5.5% vs 7.3%2 |
| Missed dose | Missed by less than 3 months: give it and keep the schedule; more than 3 months: start a new schedule1 | Within 7 days, inject and keep the schedule; later, depends on the schedule2 |
| Common side effects | Injection site reactions 8% vs 2% on placebo; joint pain 5% vs 4%1 | Common cold symptoms 10.5% vs 9.6%; upper respiratory infection 9.3% vs 6.3%2 |
| Storage | Room temperature, 68 F to 77 F1 | Fridge; up to 30 days at 68 F to 77 F2 |
| Boxed warning | None1 | None2 |
Leqvio's three main trials ran 18 months in adults on maximum-tolerated statins. At day 510, LDL fell 52% more than placebo in ORION-10 (heart or blood vessel disease), 50% more in ORION-11 (disease or higher risk) and 48% more in ORION-9 (HeFH). People already taking PCSK9 inhibitors were excluded.1 The Leqvio label notes that outcome trials of statins and of PCSK9 antibodies have shown that lowering LDL lowers heart-event risk, but it reports no heart-event trial of Leqvio itself.1
Repatha has two placebo-controlled outcome trials. In FOURIER (27,564 adults with established disease, median 26 months), main events happened in 9.8% vs 11.3%. In VESALIUS-CV (12,206 high-risk adults with no prior heart attack or stroke, median 55 months), heart disease death, heart attack or ischemic stroke happened in 5.5% vs 7.3%.2 These numbers come from separate trials with different people, lengths and methods, so they are not a head-to-head comparison.
The Leqvio label also says it may harm an unborn baby based on how it works, and to stop it when pregnancy is recognized or weigh ongoing need.1
Which, if either, fits is for your prescriber. More detail: Leqvio side effects, Repatha side effects, the Leqvio and Repatha dosing schedules, the Leqvio and Repatha missed-dose pages, LDL cholesterol, and Praluent vs Repatha: how do the two PCSK9 inhibitors differ?.